Intake of high fat diet is steadily increasing with the recent westernization of the Japanese life style. According to the report of the National Health and Nutrition Survey of 2008, proportion of the energy taken from the lipid in the entire energy intake is 24.9% on the average and people with high triglyceride level (greater than 110 mg/dl) or high cholesterol value (greater than 200 mg/dl) have reached about 50 to 60% at the age of 40 or higher (see Non-Patent Literature 1).
Obesity caused by the condition such as excessive fat intake has become a great social concern due to the increase in the number of patients and health risk. The obesity is the condition of excessive accumulation of adipose tissue. The standard is different by the country, and, in the diagnostic criteria of Japan Society for the Study of Obesity, obesity is defined as a body-mass index (hereinafter abbreviated as “BMI”) in excess of 25, and of such obesity, the pathological condition actually or estimated to be with the health problem caused by or associated with the obesity (at least one of 10 items including type 2 diabetes, dyslipidemia, and hypertension) and medically requiring weight decrease; and visceral fat type obesity confirmed by an umbilical CT scan with the BMI of at least 25 and doubt of upper body obesity, are defined as obesity syndrome (see Non-Patent Literature 2).
The body weight gain (obesity) caused by such cause is a risk factor for the onset of metabolic syndrome observed as dyslipidemia (which is hypercholesterolemia or hypertriglyceridemia (hereinafter also abbreviated as “hyper TG”), this also applies to the following description), hypertension, arteriosclerosis, diabetes, and obesity, and prevention of the body weight gain (obesity) is important for the prevention of the metabolic syndrome. The metabolic syndrome induces vascular complication such as peripheral vascular insufficiency, ischemic heart disease, and cerebral infarction, and the quality of life will be markedly impaired for the rest of life (see Non-Patent Literature 3).
Obesity is divided into two types, namely, essential obesity (simple obesity) and symptomatic obesity (concomitant obesity) depending on the cause. The essential obesity is the obesity caused by the accumulation of the excessive energy in the form of fat and this takes place when energy intake is in excess of the consumed energy. At least 90% of the obesity is said to be this type. Examples of the cause of such obesity include lack of exercise, wrong feeding pattern, stress, dyslipidemia (lipid metabolism disorder), excessive secretion of insulin, increase of adipocyte, and insufficiency of brown adipocyte. On the other hand, onset of the symptomatic obesity is induced by other diseases such as endocrinological obesity, hereditary obesity, hypothalamic obesity, and pharmacological obesity (see Non-Patent Literature 4).
The essential obesity is divided into two types by the location of the fat, and these two types are obesity due to subcutaneous fat (peripheral obesity) and abdominal visceral fat obesity (central obesity). The subcutaneous fat is the fat immediately below the skin, and the subcutaneous fat is often associated with an increased number of adipocytes. On the other hand, the abdominal visceral fat is the fat accumulated in the mesenterium in the peritoneal cavity, and the fat is likely to be accumulated in each adipocyte. Increased abdominal visceral fat is likely to induce metabolic abnormality, and diseases such as diabetes, hypertension, arteriosclerosis, hyperlipidemia, and fatty liver are said to be easily induced under such condition.
Fatty liver is the condition of excess accumulation of fat (and mainly neutral fat or triglyceride) in the liver, and in particular, in the hepatocyte. In medicine, fatty liver means the condition wherein lipid vacuole is found in at least 30% of the hepatocyte; the condition wherein the hepatocyte contains at least 10% by weight of the fat; or the condition wherein lipid droplet in the hepatocyte is found in at least ⅓ of the hepatocytes. The fatty liver also means the condition involving the enhancement of hepatic lipogenesis in the liver, which is the cause of the onset of the fatty liver. (See Non-Patent Literatures 5 and 6).
Typical causes of the fatty liver are overnutrition, obesity, excessive alcohol intake, and diabetes, while the fatty liver is also caused by other endocrine disorders and metabolic diseases, intake of particular drugs, and on rare occasion, by excessive undernutrition. More specifically, typical causes of the fatty liver include: (1) excessive intake of dietary fat and sugar, (2) enhanced lipogenesis in the liver, (3) enhanced triglyceride formation in the liver, (4) dysfunction of the decomposition of fatty acid and triglyceride in the liver, (5) increase in the amount of free fatty acid flowing into the liver, and (6) defect of lipoprotein secretion from the liver into the blood (see Non-Patent Literatures 5 and 6).
The body weight gain (obesity) can be efficiently prevented by consumption of the ingested calories through exercise and/or decrease of calory intake by dietary restriction. The dietary restriction can be accomplished only by strict nutrition education and control, and reliable dietary restriction in normal life would be associated with considerable difficulty. Drug therapy, which may be another choice, is associated with the problems of side effects. Accordingly, if accumulation of the dietary fat in the body can be suppressed in a safe and healthy way, such method would be a practical and useful choice in treating the obesity and related diseases (for example, dyslipidemia, hypertension, arteriosclerosis, and diabetes) and promoting the health.
Despite many reports on influence of the ω3 fatty acid on the obesity (see, for example, Non-Patent Literature 7), there is obviously plenty of scope for investigation. Bryhn et al. reports an experiment conducted by administering a ω3 fatty acid composition (a mixture of icosapentaenoic acid (hereinafter abbreviated as “EPA”) and docosahexaenoic acid (hereinafter abbreviated as “DHA”)) to the mouse which had been fed on a high fat diet to thereby suppress the body weight gain. However, they failed to properly identify the effective component, and argued that DHA was the substance that contributed for the activity of suppressing the body weight gain (see Patent Literature 1).
Sato et al. reports that high purity ethyl icosapentate (hereinafter abbreviated as “EPA-E”) was effective in suppressing the body weight gain in a model mouse which had been continuously fed on a high-fat and high-sugar diet suffering from obesity associated with enhanced hepatic lipogenesis or fatty liver while it was ineffective in a model mouse which had been continuously fed on a high-fat diet suffering from obesity not associated with the enhancement of hepatic lipogenesis or fatty liver (see Non-Patent Literature 8).
Hamster is an animal which has been reported to be quite suitable in studying the regulation and mechanism of the influence of the diet on the lipid-related parameters (body weight and plasma lipid markers). The observation in hamsters has also been reported to correspond to the phenomena in human (See Non-Patent Literature 9, 10, or 11).
There is a report that, in human plasma, high-density lipoprotein cholesterol value (hereinafter abbreviated as “HDL-C value”) is regulated by the cholesteryl ester transfer protein (hereinafter abbreviated as “CETP”). CETP activity is little found in mouse, rat, and dog while its presence has been confirmed in hamster, rabbit, and monkey, and investigation on the CETP activity has been conducted based on such finding (see Non-Patent Literature 12).